Sucralfate modulates uPAR and EGFR expression in an experimental rat model of cervicitis.

Sucralfate is a drug used in the treatment of gastric and duodenal ulcer; it is cytoprotective and able to increase the bioavailability of several growth factors, modulating the wound healing process. In this study we tested the possible therapeutic effect of Sucralfate in the treatment of ulcerative lesions occurring in uterine cervix; to investigate such effect we used an experimental rat model of cervicitis in which the uPAR and EGFR expression were evaluated. Cervicitis was induced in wild and ovariectomized Wistar female rats by an acetic acid-soaked tampon. The animals were divided into two main groups (4 and 7 days) and Sucralfate was administered topically until the day they were sacrificed. In order to distinguish physiological and drug-induced healing, quantitative and qualitative uPAR and EGFR expression were evaluated by using Western blot and Immunohistochemistry techniques. Western blot analysis demonstrated an increased expression of both receptors after 4 days from wounding in wild and ovariectomized animals. In particular in ovariectomized animals the expression of uPAR and EGFR increased after 4 days while it reduced following the administration of Sucralfate. In wild rats the same was observed for uPAR expression, while EGFR was different; in fact, its expression increased significantly at day 4 in the animals treated with the drug and only at day 7 in those untreated. Immunohistochemistry highlighted a noteworthy epithelial colocalization of EGFR and uPAR after 4 days in the animals treated with Sucralfate. We conclude that Sucralfate can promote the healing of ulcerative cervicitis and moreover, it reduces the normal healing time because of its modulatory property on uPAR and EGFR expression.

Treatment with 1,25-dihydroxyvitamin D3 preserves glomerular slit diaphragm-associated protein expression in experimental glomerulonephritis.

In this study, we investigated the effect of 1,25(OH)2D3 on proteinuria and on the alteration of slit diaphragm-associated proteins induced by anti-Thy 1.1 in Wistar rats. Four groups of animals were studied: group I, anti-Thy 1.1 treated rats; group II, anti-Thy1.1 treated group that at day 2, after the onset of overt proteinuria, started the treatment with 1,25(OH)2D3; group III, normal control rats injected with vehicle alone; group IV, rats that received only 1,25(OH)2D3. At day 2, in group I and II, before the administration of 1,25(OH)2D3, protein excretion was significantly increased when compared to controls. Overt proteinuria was maintained until day 14 in group I whereas in group II protein excretion was significantly reduced from day 3 to day 14. Moreover, treatment with 1,25(OH)2D3 abrogated podocytes injury, detected as desmin expression and loss of nephrin and zonula occludens-1 (ZO-1), two slit diaphragm-associated proteins, and glomerular polyanion staining, that were observed in group I. In conclusion, these results suggest that 1,25(OH)2D3 administrated with a therapeutic regiment may revert proteinuria, counteracting glomerular podocyte injury.

Wine, sirtuins and nephroprotection: not only resveratrol.

Resveratrol (RSV), a red wine component, and red wine itself exert cardio- and nephroprotective effects by modulating the Nitric Oxide system (NO). It has been shown that one of the main actions resulting from NO modulation is sirtuin regulation, especially SIRT-1 regulation. Elucidating both upstream and downstream molecular mechanisms of the SIRT-1 pathway is an open field of investigation that can explain its role not only in long-term processes, such as aging, but also in short-term processes, such as protection against ischemic damage. Our hypothesis suggests the importance of investigating compounds that are routine dietary components and do not necessarily contain RSV. Their nephroprotective activity could involve not only eNOS-dependent, but also NO-dependent but eNOS-independent mechanisms, or other molecular alternative signaling systems.

Immunomodulatory activity of shikimic acid and quercitin in comparison with oseltamivir (Tamiflu) in an in vitro model.

The risk of an avian influenza pandemic has put oseltamivir (Tamiflu) in the spotlight and has given rise to rumors that shikimic acid (SK), which is used for the synthesis of Tamiflu, possesses therapeutic activity. This study was undertaken to determine whether SK, either alone or in combination with quercitin (QT) is able to modulate the release of IL-6 and IL-8 from peripheral blood mononuclear cells (PBMCs). The experiments were conducted comparing the properties of SK, both alone and in combination, with those of Tamiflu. The incubation of PBMCs with 100 nM Tamiflu or SK at two concentrations (10 nM; 100 nM) did not produce any change in IL-6 and IL-8 baseline levels (data expressed as incremental change vs. baseline). On the contrary, incubation with SK and QT at both concentrations (10 and 100 nM) produced a significant increase in the release of IL-8 as compared to other groups (4.19 +/- 0.82, SK-QT 10 nM; 3.83 +/- 1.17 SK-QT 100 nM, P < 0.05 vs. baseline 1.00 +/- 0.10, Tamiflu 100 nM 1.35 +/- 0.16, SK 10 nM 1.68 +/- 0.15 and SK 100 nM 1.80 +/- 0.48). The SK-QT combination also proved to be effective in the upregulation of IL-6 (3.08 +/- 0.46, SK-QT 10 nM; 3.60 +/- 0.74 SK-QT 100 nM, P < 0.05 vs. baseline 1.00 +/- 0.26). According to these findings SK alone is not able to modulate innate immunity in antiviral terms. However, the data show that the SK + QT combination, even at low doses, may be effective for the modulation of innate immunity.